There is an increasing drive towards the miniaturization of scientific and technological devices. This push began in electronics, with the advent of integrated circuits. More recently micromechanical and microfluidic devices have gained increasing attention. Microfluidic systems make it possible to miniaturize entire instruments, increasing portability while decreasing cost. Microfluidics are finding many applications in scientific and biomedical instrumentation and consumer devices. Microfluidic devices are widely used for biological assays and analytical processes. Such devises are used in ELISA techniques, in DNA and RNA arrays, and to facilitate combinatorial chemistry reactions. Microfluidic devices have been designed to serve as sensors, fluid distribution systems, reaction arrays, and “mini-factories.” Microfluidic devices are discussed in U.S. Pat. Nos. 6,418,968; 6,251,343; 6,086,740; U.S. Patent Publications Nos. 20070157739; 20070145263; 20070151335; 20070141721; EP-A-1129772; and WO00/60352; WO02/11887; WO96/15576.
Conventional microfluidic systems that are used with aqueous media are often fabricated from polydimethylsiloxane (PDMS). Fabrication begins with the deposition of a thick layer of photoresist, such as SU-8, on a flat substrate. The photoresist is then exposed and developed, leaving a pattern of constant height that is in the shape of the desired channels. The pattern is then immersed in liquid PDMS resin, which is subsequently cured to turn it into an elastomeric solid. The cured PDMS is removed from the substrate and can be treated with an oxygen plasma and then bonded to another substrate to create the microfluidic system. The original master pattern can be used repeatedly to create many micro fluidic systems.
Due to constraints in fabrication techniques, the channels formed in such networks generally lie within a single plane or, at most, within two adjacent planes. Devices with truly three-dimensional channel geometries can be fabricated only with great difficulty, in a process that requires layer-by-layer construction and careful registration (e.g., careful cutting and stacking of layers of PDMS patterned in this manner) at each step (e.g., U.S. Patent Publication No. 20070139451).
Advances in conventional lithography have been responsible for enormous gains in the power of microelectronic devices in the past few decades. The realization that the same lithographic techniques could be applied to micromachines has led to a parallel revolution in microelectromechanical systems (“MEMS”) (Lafratta, C. N. et al. (May 23, 2006) “Soft-Lithographic Replication Of 3D Microstructures With Closed Loops,” Proc. Natl. Acad. Sci. (USA) 103(23):8589-8594; Rai-Coudhury, P. (1997) HANDBOOK OF MICROLITHOGRAPHY, MICROMACHINING, & MICROFABRICATION (SPIE Optical Engineering Press, Bellingham, Wash.); Moore, D. F. et al. (1999) “Recent Developments In Micromachined Silicon,” Electron. Commun. Eng. J. 11:261-270; WO 2006/093963). However, the fact that conventional lithographic techniques are limited in their ability to create features with significant structure in the dimension perpendicular to the substrate on which fabrication is performed constitutes a fundamental limitation for the development of MEMS devices.
Newer lithographic techniques, such as “LIGA” (Malek, C. K. et al. (2004) “Applications Of LIGA Technology To Precision Manufacturing Of High-Aspect-Ratio Micro-Components And -Systems: A Review, Microelectron. J. 35:131-143), multiphoton absorption polymerization (“MAP”) (Campagnola, P. J. et al. (2000) “3-Dimensional Submicron Polymerization of Acrylamide by Multiphoton Excitation of Xanthene Dyes,” Macromolecules 33:1511-1513; Maruo, S. et al. (1997) Opt. Lett 22:132-134; Kawata, S. et al. (2001) “Finer Features For Functional Microdevices,” Nature 412:697-698; Cumpston, B. H. et al. “Two-Photon Polymerization Initiators For Three-Dimensional Optical Data Storage And Microfabrication,” (1999) Nature 398:51-54; Sun, H. B. et al. (2003) “,” J. Lightwave Technol. 21:624-633; Baldacchini, T. et al. (2004) In: ENCYCLOPEDIA OF NANOSCIENCE AND NANOTECHNOLOGY; Schwarz, J. A. et al. (Eds.) Marcel Dekker, New York, pp. 3905-3915; Witzgall, G. et al. (1998) Opt. Lett 23:1745-1747; Belfield, K. D. et al. (2000) “Near-IR Two-Photon Photoinitiated Polymerization Using a Fluorone/Amine Initiating System,” J. Am. Chem. Soc 122:1217-1218; Serbin, J. et al. (2003) “Femtosecond Laser-Induced Two-Photon Polymerization Of Inorganic-Organic Hybrid Materials For Applications In Photonics,” Opt. Lett. 28:301-303), and multibeam interference lithography (“MBIL”) (Yang, S. et al. (2002) “Creating Periodic Three-Dimensional Structures by Multibeam Interference of Visible Laser,” Chem. Mater 14:2831-2833; Ullal, C. K. et al. (2003) “,” J. Opt. Soc. Am. A 20:948-954; Moon, J. H. et al. (2005) J. Macromol. Sci.-Polymer Rev. C45:351-373; Chan, T. Y. M. et al. (2005) Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Top 71:046605) also have limited applicability to the production of complex 3D structures.
LIGA is a parallel procedure, but unable to make arbitrarily complex 3D microdevices. MAP is an inherently serial procedure. Structures are created on a voxel-by-voxel basis, and so fabrication on the wafer scale is a slow process. Although MBIL is a highly parallel technique, it can only be used to fabricate periodic structures with spatial periods on the scale of the wavelength of the light used. As a result, none of these techniques is suitable for the mass production of arbitrarily complex 3D microdevices (Lafratta, C. N. et al. (May 23, 2006) “Soft-Lithographic Replication Of 3D Microstructures With Closed Loops,” Proc. Natl. Acad. Sci. (USA) 103(23):8589-8594).
Microtransfer molding (“μTM”) procedures have also been explored. In such procedures, one pours an elastomeric resin (e.g., polydimethylsiloxane (“PDMS”)) over a master structure and then cures it (Xia, Y. et al. (1998) “Soft Lithography,” Angew. Chem. Int. Ed 37:550-575; Xia, Y. et al. (1998) “Soft Lithography,” Annu. Rev. Mater. Sci 28:153-184; Gates, B. D. et al. (2005) “New Approaches to Nanofabrication: Molding, Printing, and Other Techniques,” Chem. Rev 105, 1171-1196). The mold is then released from the master, filled with a molding material, and pressed against another substrate. The molding material is then cured and the mold released, leaving a replica of the master structure. Microtransfer molding has been used to create wafer-scale replicas of master structures that were created with conventional lithography and to replicate 3-D structures created with MAP (LaFratta, C. N. et al. (2004) “Replication of Two-Photon-Polymerized Structures with Extremely High Aspect Ratios and Large Overhangs,” J. Phys. Chem. B; 2004; 108(31) pp 11256-11258). Because of the elastic nature of the PDMS mold, it is possible to replicate a wide range of structures, including ones with high aspect ratios or substantial overhangs (LaFratta, C. N. et al. (2004) “Replication of Two-Photon-Polymerized Structures with Extremely High Aspect Ratios and Large Overhangs,” J. Phys. Chem. B; 2004; 108(31) pp 11256-11258; Rogers, J. A. (2003) In: THREE-DIMENSIONAL NANOENGINEERED ASSEMBLIES; Orlando, T. M. et al. (Eds.) Materials Res. Soc., Warrendale, Pa., Vol. 739, pp. H.1.2.1).
One deficiency of μTM method is that if the master structure contains a closed loop (such as an arch), when the elastomeric resin is poured over the loop and cured, the loop will be topologically “locked” within the elastomer and thus cannot be released. Thus, closed loop structures cannot be replicated in a single step with μTM. As a result, the molding of closed loops continues to require a layer-by-layer fabrication approach (Gates, B. D. et al. (2005) “New Approaches to Nanofabrication: Molding, Printing, and Other Techniques,” Chem. Rev 105, 1171-1196; Rogers, J. A. (2003) In: THREE-DIMENSIONAL NANOENGINEERED ASSEMBLIES; Orlando, T. M. et al. (Eds.) Materials Res. Soc., Warrendale, Pa., Vol. 739, pp. H.1.2.1); Unger, M. A. et al. “Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography,” (2000) Science 288(5463):113-116) that has not been satisfactory (Lafratta, C. N. et al. (May 23, 2006) “Soft-Lithographic Replication Of 3D Microstructures With Closed Loops,” Proc. Natl. Acad. Sci. (USA) 103(23):8589-8594; WO 2006/093963).
In sum, the ability to create truly 3-D microfluidic systems would enable the fabrication of new types of devices and permits one to make existing devices more compact. Unfortunately, current methods of fabrication of 3-D microfluidic networks requires a time-consuming and complex layer-by-layer assembly, involving a delicate registration step at each layer. As a result, 3-D microfluidic systems cannot presently be produced at attractive costs. Thus, a need remains for a technology capable of forming a 3-D microfluidic network in a single step. The present invention is directed to this and related needs.